Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding
Lawrence P. Andrews, Ashwin Somasundaram, Jessica Moskovitz, Andrea L. Szymczak-Workman, Chang Liu, Anthony R. Cillo, Lin Huang, Daniel P. Normolle, Kelly D. Moynihan, Ichiro Taniuchi, Darrell J. Irvine, John M. Kirkwood, Evan J. Lipson, Robert L. Ferris, Tullia C. Bruno, Creg J. Workman, Dario A.A. Vignali
Abstract
in the peripheral blood of patients with head and neck squamous cell carcinoma, which corresponded with poor prognosis. This correlation was also observed in a cohort of patients with skin cancers and was associated with increased disease progression after standard-of-care immunotherapy. These data suggest that subtle changes in LAG3 inhibitory receptor signaling can act as a resistance mechanism with a substantive effect on patient responsiveness to immunotherapy.